Viral Persistence Research Articles

Contemporary Treatment Practices for Subacute Sclerosing Panencephalitis: A Nationwide Survey Among Adult and Pediatric Neurologists in India.

Subacute sclerosing panencephalitis (SSPE) is a progressive disorder caused due to the persistence of mutant measles virus in the brain. Treatment strategies for SSPE remain largely undefined, and there exists no information on how neurologists are currently managing SSPE. A survey-based study was conducted among Indian neurologists managing pediatric and adult patients with SSPE. A questionnaire-based survey was circulated by email regarding respondent demographics, preference for disease-modifying strategies, and symptomatic therapy. Survey response was obtained from 298 neurologists (responder rate 9.5%) and eventually analyzed from 266 respondents who managed SSPE in routine practice. This included 222 (83.5%) adult and 44 (16.5%) pediatric neurologists from 21 states of India. Ninety-five respondents (35.7%) indicated that they always advised Isoprinosine (inosine pranobex) to their patients. Regarding interferon therapy, 121 (45.5%) reported never advising it, whereas 56 (21.1%) always advised it. For myoclonus, the most frequently used first-line drug was valproate (181, 68%), followed by levetiracetam (58, 21.8%). Most (150, 56.4%) of the respondents favored personalized therapy for the individual patient in terms of the duration of disease-modifying treatment. The patient follow-up was reported to be poor, with most (171, 64.3%) of the patients following up only occasionally and 24 (9%) respondents indicating that patients are lost to follow-up promptly after the initial visit. While SSPE remains a vaccine-preventable illness and the focus should be on prevention through vaccination, there is an unmet urgent need among Indian neurologists for better-defined treatment strategies for patients with SSPE.

Dynamic analysis of an HIV model with CTL immune response and logarithmic Ornstein–Uhlenbeck process

In this paper, we present a stochastic HIV model, including logistic growth, CTL immune response and logarithmic mean–reverting Ornstein–Uhlenbeck process. Firstly, we certify that there exists a unique global positive solution by rigorous mathematical analysis. Then, by constructing a suitable Lyapunov function and using the strong law of large numbers and Fatou’s lemma, we obtain the existence of the stationary distribution when stochastic reproduction number is greater than one. Moreover, we derive an approximate expression for the probability density function of the stochastic model around the infected equilibrium of its corresponding deterministic model. In addition, a critical condition for virus extinction is established. Finally, through numerical simulations, we investigate the effects of noise intensity and the logistic growth on model behavior, and we also explore the influence of key parameters on virus persistence and extinction.

The Spectrum of Cutaneous Granulomatous Inflammation and Detection of Rubella Virus in Skin Biopsies of Patients With Common Variable Immune Deficiency.

There is a known association between common variable immunodeficiency (CVID) and granulomas in multiple organ systems, including the skin, lung, liver, and spleen. Rubella virus has also been detected within cutaneous granulomas in both immunocompetent and immunocompromised hosts. We present a retrospective case series of patients with CVID and granulomatous skin disease and describe the spectrum of clinical and histopathologic features, including the status of rubella virus in the cutaneous granulomas. We retrospectively reviewed the clinical and histopathological characteristics of patients diagnosed with CVID at our institution, with cutaneous findings and skin biopsies available for review between 1990 and 2023, demonstrating granulomatous inflammation. Eight patients met the inclusion criteria. The most common histopathologic pattern was palisaded granulomatous inflammation, seen in five of eight cases. Three cases showed strictly sarcoidal granulomas. Background inflammation was peri-granulomatous (8/8) and the predominant background inflammatory cell type was lymphocytic (6/8). Rubella virus testing was performed for seven of eight cases and found to be positive in one case. Cutaneous granulomatous disease in CVID can present with a spectrum of clinical morphologies, granulomatous patterns, and variable rubella virus persistence. Dermatopathologists should be aware of the spectrum of findings when considering cutaneous CVID-related granulomatous disease in the differential diagnosis.

The consequences of SARS-CoV-2 within-host persistence

The consequences of SARS-CoV-2 within-host persistence

Hepatitis B and D virus entry.

Hepatitis B virus (HBV) entry is the initial step of viral infection, leading to the formation of covalently closed circular DNA, which is a molecular reservoir of viral persistence and a key obstacle for HBV cure. The restricted entry of HBV into specific cell types determines the nature of HBV, which has a narrow host range in tissues and species. Hepatitis D virus (HDV) shares viral surface antigens with HBV and thus follows a similar entry mechanism at its early stages. In late 2012, sodium taurocholate cotransporting polypeptide was discovered as an HBV and HDV entry receptor. Since then, the mechanisms of HBV and HDV entry have been extensively analysed. These analyses have expanded our understanding of HBV and HDV host tropism and have provided new strategies for the development of antiviral agents. Notably, the structures of sodium taurocholate cotransporting polypeptide and its interaction with the 2-48 amino acid region of viral preS1 have been recently solved. These findings will stimulate further entry studies. In this Review, we summarize current understanding of HBV and HDV entry and future perspectives.

Self-replicating recombinant virus-like particles of lentivirus proliferating in glioblastoma cells and normal human macrophages

Introduction. Both attenuated and inactivated vaccines are used in disease control. Inactivated vaccines are very diverse and include whole cell and acellular vaccines containing protein target antigens or nucleic acids encoding target antigens. Immunity induced by inactivated vaccines is not believed to be long-lasting. It is very problematic to develop a vaccine against viruses that integrate into the genome of the host cell, as well as against persistent viruses that penetrate the central nervous system (CNS), which is typical for the human immunodeficiency virus type 1 (HIV-1). Aim of the study: to evaluate the possibility of forming HIV-1 recombinant virus-like particles (recVLPs) and HIV-1B recombinant VLPs and simian immunodeficiency virus (SIV) — SHIV89.6P based on self-replicating RNAs (srRNAs) producing target lentivirus antigens on the alphavirus replicon platform (Sindbis virus or Venezuelan equine encephalomyelitis virus (VEEV)), and also to evaluate the ability of HIV-1B and SHIV89.6P VLPs to infect glioblastoma cells and normal human macrophages. Materials and methods. BHK-21 cells were transfected with the srRNA mixture by electroporation. Recombinant virus-like particles (recVLP’s) in recVLP’s-infected cells were detected using the immunofluorescence assay (ELISA) and electron microscopy. recVLP’s were used to infect glioblastoma cells and normal macrophages from a healthy donor. Results. Based on the genomic RNA of the alphavirus, the plasmids were created, transcription from which makes it possible to obtain RNA that expresses lentiviral gene products in cells in quantities sufficient for the formation of mature VLPs. In BHK-21 cells infected with recVLP’s, virus-specific antigens are detected only in the cytoplasm, but not in the nucleus. Both glioblastoma cells (U87) and normal human macrophages containing CD4 receptor and SSR5 and CXR4 co-receptors give infectious progeny of HIV-1B and SHIV89.6P recVLP’s when infected with supernatant obtained after transfection of BHK-21 cells with srRNA. Discussion. The results obtained show the possibility of expressing lentivirus structural proteins in glioblastoma cells (U87) and in normal human macrophages and can be used in the future to study the presentation of antigens in native and functional conformations in appropriate model systems to study the possibility of suppressing HIV infection in viral reservoirs in the CNS.

A novel picorna-like virus in the flatworm Stenostomum leucops (Catenulida).

We present the genome sequence and organization and evidence of persistence of a new picorna-like virus infecting the flatworm Stenostomum leucops. The complete genome sequence belongs to a virus with a positive single-stranded RNA genome with two open reading frames (ORFs) flanked by untranslated regions and a polyadenylated C-terminus. The ORFs encode proteins with conserved motifs typical of members of the order Picornavirales. Phylogenetic analysis confirmed membership in this viral order, and it was found to be closely related to viruses found in Biomphalaria (Mollusca) in France and a virus detected in a metagenomic analysis of water sources from the USA, suggesting widespread distribution. RT-PCR analysis revealed that this virus can be detected in a laboratory-grown worm isolate for at least five years, suggesting persistent infection. However, no apparent deleterious effects were observed in the worms in culture, suggesting a possible commensal relationship between the virus and the worms.

Type I interferon signaling in dendritic cells limits direct antigen presentation and CD8+ T cell responses against an arthritogenic alphavirus.

Ross River virus (RRV) and other alphaviruses cause chronic musculoskeletal syndromes that are associated with viral persistence, which suggests deficits in immune clearance mechanisms, including CD8+ T-cell responses. Here, we used a recombinant RRV-gp33 that expresses the immunodominant CD8+ T-cell epitope of lymphocytic choriomeningitis virus (LCMV) to directly compare responses with a virus, LCMV, that strongly induces antiviral CD8+ T cells. After footpad injection, we detected fewer gp33-specific CD8+ T cells in the draining lymph node (DLN) after RRV-gp33 than LCMV infection, despite similar viral RNA levels in the foot. However, less RRV RNA was detected in the DLN compared to LCMV, with RRV localizing principally to the subcapsular region and LCMV to the paracortical T-cell zones. Single-cell RNA-sequencing analysis of adoptively transferred gp33-specific transgenic CD8+ T cells showed rapid differentiation into effector cells after LCMV but not RRV infection. This defect in RRV-specific CD8+ T effector cell maturation was corrected by local blockade of type I interferon (IFN) signaling, which also resulted in increased RRV infection in the DLN. Studies in Wdfy4-/-, CD11c-Cre B2mfl/fl, or Xcr1-Cre Ifnar1fl/fl mice that respectively lack cross-presenting capacity, MHC-I antigen presentation by dendritic cells (DCs), or type I IFN signaling in the DC1 subset show that RRV-specific CD8+ T-cell responses can be improved by enhanced direct antigen presentation by DCs. Overall, our experiments suggest that antiviral type I IFN signaling in DCs limits direct alphavirus infection and antigen presentation, which likely delays CD8+ T-cell responses.IMPORTANCEChronic arthritis and musculoskeletal disease are common outcomes of infections caused by arthritogenic alphaviruses, including Ross River virus (RRV), due to incomplete virus clearance. Unlike other viral infections that are efficiently cleared by cytotoxic CD8+ T cells, RRV infection is surprisingly unaffected by CD8+ T cells as mice lacking or having these cells show similar viral persistence in joint and lymphoid tissues. To elucidate the basis for this deficient response, we measured the RRV-specific CD8+ T-cell population size and activation state relative to another virus known to elicit a strong T-cell response. Our findings reveal that RRV induces fewer CD8+ T cells due to limited infection of immune cells in the draining lymph node. By increasing RRV susceptibility in antigen-presenting cells, we elicited a robust CD8+ T-cell response. These results highlight antigen availability and virus tropism as possible targets for intervention against RRV immune evasion and persistence.

Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.

Persistence With Human Immunodeficiency Virus Pre-exposure Prophylaxis in an Active-Duty Military Population.

There is limited data on Human Immunodeficiency Virus Pre-exposure Prophylaxis (PrEP) use and persistence in the military. Despite universal access to care, there is concern that PrEP persistence may be lower in military populations due to logistical challenges and perceived stigma. This study evaluated the persistence rates as well as reasons for PrEP discontinuation in a military cohort. This study evaluated all active-duty service members who received PrEP between 2020 and 2022 at a large military infectious diseases clinic. All charts were examined to determine patient characteristics. Patients who discontinued PrEP were contacted to determine the reason for discontinuation and invited to restart PrEP. In total, 112 service members received PrEP during the study period. The cohort was predominantly male (99%) with a median age 30 [IQR: 26-34] and a median of 2 years [IQR: 0-3] receiving PrEP. The most common indication was multiple sexual partners with less than 100% condom use (88%). At the end of the study, most (79%) patients were still receiving PrEP including 33 (37%) at other facilities. Of the twenty-four service members who were no longer receiving PrEP, 18 (75%), were able to be contacted. No patients contacted were interested in restarting PrEP. In this cohort with universal access to care, PrEP persistence rates were greater than seen in other populations. While the most common reason for discontinuation was changes in sexual behavior, systemic factors still contributed to PrEP discontinuation. Future studies should elucidate the challenges to PrEP care in the military.

Viral intruders in the heart: A review of RNA viruses and their role in cardiac disorders.

Viral cardiac diseases have a significant impact on global health, and RNA viruses play a crucial role in their pathogenesis. This literature review aims to provide a comprehensive understanding of the complex relationship between RNA viruses and cardiac diseases, focusing on the molecular processes and clinical implications of these interactions. The paper begins by discussing the various RNA viruses that have been linked to cardiac infections. Subsequently, the study explores the mechanisms through which RNA viruses can cause cardiac injury, including direct viral invasion, immune-mediated responses, and molecular mimicry. The review extensively examines the intricate interplay between the host immune system and RNA viruses, shedding light on both protective and harmful immune responses. Additionally, it investigates the role of viral persistence and chronic inflammation in the long-term effects on cardiac health. The thorough analysis presented not only enhances our scientific understanding of how RNA viruses contribute to the development of cardiac diseases but also highlights potential avenues for future research and breakthroughs in this field. Given the significant global health threat posed by viral cardiac disorders, unraveling the molecular foundations of these diseases is essential for advancing diagnostic capabilities and therapeutic interventions.

UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma.

A newly discovered E3 ubiquitin ligase, UBR7, plays a crucial role in histone H2BK120 monoubiquitination. Here, we report a novel function of UBR7 in promoting hepatitis B virus (HBV) pathogenesis, which further leads to HBV-induced hepatocellular carcinoma (HCC). Transcriptomics analysis from HCC patients revealed the deregulation of UBR7 in cancer. Remarkably, targeting UBR7, particularly its catalytic function, led to a significant decrease in viral copy numbers. We also identified the speckled family protein Sp110 as an important substrate of UBR7. Notably, Sp110 has been previously shown to be a resident of promyelocytic leukemia nuclear bodies (PML-NBs), where it remains SUMOylated, and during HBV infection, it undergoes deSUMOylation and exits the PML body. We observed that UBR7 ubiquitinates Sp110 at critical residues within its SAND domain. Sp110 ubiquitination downregulates genes in the type I interferon response pathway. Comparative analysis of RNA-Seq from the UBR7/Sp110 knockdown data set confirmed that the IFN-β signaling pathway gets deregulated in HCC cells in the presence of HBV. Single-cell RNA-Seq analysis of patient samples further confirmed the inverse correlation between the expression of Sp110/UBR7 and the inflammation score. Notably, silencing of UBR7 induces IRF7 phosphorylation, thereby augmenting interferon (IFN)-β and the downstream interferon-stimulated genes (ISGs). Further, wild-type but not the ubiquitination-defective mutant of Sp110 could be recruited to the type I interferon response pathway genes. Our study establishes a new function of UBR7 in non-histone protein ubiquitination, promoting viral persistence, and has important implications for the development of therapeutic strategies targeting HBV-induced HCC.

Stress from environmental change drives clearance of a persistent enteric virus.

Persistent viral infections are associated with long-term health issues and prolonged transmission. How external perturbations after initial exposure affect the duration of infection is unclear. We discovered that murine astrovirus, an enteric RNA virus, persists indefinitely when mice remain unperturbed but is cleared rapidly after cage change. Besides eliminating the external viral reservoir, cage change also induced a transcriptional defense response in the intestinal epithelium. We further identified that displacing infected animals initially caused a temporary period of immune suppression through the stress hormone corticosterone, which was followed by an immune rebound characterized by an increase in CD8 T cells responsible for the epithelial antiviral responses. Our findings show how viral persistence can be disrupted by preventing re-exposure and activating immunity upon stress recovery, indicating that external factors can be manipulated to shorten the duration of a viral infection.

Pathophysiology of Adipose Tissue Macrophages indicating a potential reservoir site for HIV infection that might be troublesome to eradicate HIV-1

Human Immunodeficiency Virus Type 1 (HIV-1) is a condition that affects over 60 million people worldwide. Viral infection can be controlled using highly active antiretroviral therapy (HAART) to suppress HIV-1 replication and hinder disease progression, but viremia quickly rebounds following HAART interruption. It is highly likely that the persistence of virus occurs predominantly in latently infected CD4+ T cells, a new strategy to eradicate HIV-1. Previously it has been shown that the viral reservoir is seeded rapidly following the initial infection of rhesus macaques with SIV, even before the establishment of a systemic infection, so destroying this reservoir may be vital to the effective clearance of HIV. We reasoned that long-lived tissue macrophages contribute significantly to the SIV/HIV reservoir, such as those that may be found in adipose tissue. Mediscope 2024;11(2): 68-72

Dengue and chikungunya virus dynamics, identification, and monitoring in wastewater.

Monitoring wastewater is an effective strategy for supporting clinical surveillance for viral infections. Wastewater monitoring, also known as wastewater-based epidemiology (WBE), uses existing wastewater collection networks to obtain a composite sample of a population that can be used to predict disease dynamics in a specific area. Viruses such as dengue and chikungunya are primarily transmitted through the bites of infected Aedes mosquito species. The prevalence of the Aedes mosquito in tropical and subtropical regions makes these diseases a serious threat to public health. Employing wastewater surveillance, monitoring, and regulating the spread of diseases like dengue and chikungunya-notably caused by mosquitoes-has been recommended. However, understanding the dynamics of viral release and its persistence in wastewater is critical for monitoring purposes. Although methods for recovering RNA for some viruses from wastewater have been developed, the same approach does not work equally well for viruses such as dengue and chikungunya due to low levels of viral RNA and susceptibility to degradation. As a result, a tailored approach to recovering these viruses from wastewater is required. This review summarizes viral release from infected hosts, its dynamics, and approaches for dengue and chikungunya wastewater surveillance. The review also identifies existing knowledge gaps in viral persistence in wastewater and recovery.

DNA Sensor ABCF1 Phase Separates With cccDNA to Inhibit Hepatitis B Virus Replication.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) contributes to viral persistence and recurrence, however, how the host innate immune system responds to cccDNA is still less known. Here, based on cccDNA-hepatic proteins interaction profiling, DNA sensor ATP-binding cassette subfamily F member 1 (ABCF1) is identified as a novel cccDNA-binding protein and host restriction factor for HBV replication. Mechanistically, ABCF1 recognizes cccDNA by KKx4 motif and forms phase-separated condensates by the poly-glutamine (PolyQ) region of the N-terminal intrinsically disordered low-complexity domain (LCD). Subsequently, ABCF1-cccDNA phase separation not only activates the type I/III interferon (IFN-I/III) pathway but also prevents Pol II accumulation on cccDNA to inhibit HBV transcription. In turn, to sustain viral replication, HBV reduces ABCF1 expression by HBx-mediated ubiquitination and degradation of SRY-box transcription factor 4（SOX4）, leading to defects in SOX4-mediated upregulation of ABCF1 transcription. Taken together, the study shows that ABCF1 interacts with cccDNA to form phase separation that dually drives innate immune signaling and HBV transcriptional inhibition. These findings shed new light on the understanding of host defense against cccDNA and provide a novel promising therapeutic strategy for HBV infection.

Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant.

Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC). Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study. 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups. 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.

ISG15 Drives Immune Pathology and Respiratory Failure during Systemic Lymphocytic Choriomeningitis Virus Infection.

ISG15, an IFN-stimulated gene, plays a crucial role in modulating immune responses during viral infections. Its upregulation is part of the host's defense mechanism against viruses, contributing to the antiviral state of cells. However, altered ISG15 expression can also lead to immune dysregulation and pathological outcomes, particularly during persistent viral infections. Understanding the balance of ISG15 in promoting antiviral immunity while avoiding immune-mediated pathology is essential for developing targeted therapeutic interventions against viral diseases. In this article, using Usp18-deficient, USP18 enzymatic-inactive and Isg15-deficient mouse models, we report that a lack of USP18 enzymatic function during persistent viral infection leads to severe immune pathology characterized by hematological disruptions described by reductions in platelets, total WBCs, and lymphocyte counts; pulmonary cytokine amplification; lung vascular leakage; and death. The lack of Usp18 in myeloid cells mimicked the pathological manifestations observed in Usp18-/- mice and required Isg15. Mechanistically, interrupting the enzymes that conjugate/deconjugate ISG15, using Uba7-/- or Usp18C61A mice, respectively, led to accumulation of ISG15 that was accompanied by inflammatory neutrophil accumulation, lung pathology, and death similar to that observed in Usp18-deficient mice. Moreover, myeloid cell depletion reversed pathological manifestations, morbidity, and mortality in Usp18C61A mice. Our results suggest that dysregulated ISG15 production and signaling during persistent lymphocytic choriomeningitis virus infection can produce lethal immune pathology and could serve as a therapeutic target during severe viral infections with pulmonary pathological manifestations.

BK Polyomavirus Infection of Bladder Microvascular Endothelial Cells Leads to the Activation of the cGAS-STING Pathway.

BK polyomavirus (BKPyV) infection in humans is usually asymptomatic but ultimately results in viral persistence. In immunocompromised hosts, virus reactivation can lead to nephropathy or hemorrhagic cystitis. The urinary tract serves as a silent reservoir for the virus. Recently, it has been demonstrated that human bladder microvascular endothelial cells (HBMVECs) serve as viral reservoirs, given their unique response to infection, which involves interferon (IFN) production. The aim of the present study was to better understand the life cycle of BKPyV in HBMVECs, uncover the molecular pathway leading to IFN production, and to identify the connection between the viral life cycle and the activation of the IFN response. Here, in the early stage of infection, BKPyV virions were found in internalized monopinocytic vesicles, while later they were detected in late endosomes, lysosomes, tubuloreticular structures, and vacuole-like vesicles. The production of viral progeny in these cells started at 36 h postinfection. Increased cell membrane permeability and peaks of virion release coincided with the leakage of viral and cellular DNA into the cytosol at approximately 60 h postinfection. Leaked DNA colocalized with and activated cGAS, leading to the activation of STING and the consequent transcription of IFNB and IFN-related genes; in contrast, the IFN response was attenuated by exposure to the cGAS inhibitor, G140. These findings highlight the importance of the cGAS-STING pathway in the innate immune response of HBMVECs to BKPyV.

Viral proteins resolve the virus-vector conundrum during hemipteran-mediated transmission by subverting salicylic acid signaling pathway

Hemipteran insects transmit viruses when infesting plants, during which vectors activate salicylic acid (SA)-regulated antiviral defenses. How vector-borne plant viruses circumvent these antiviral defenses is largely unexplored. During co-infections of begomoviruses and betasatellites in plants, betasatellite-encoded βC1 proteins interfere with SA signaling and reduce the activation of antiviral resistance. βC1 inhibits SA-induced degradation of NbNPR3 (Nicotiana benthamiana nonexpressor of pathogenesis-related genes 3), a negative regulator of SA signaling. βC1 does not bind directly to NbNPR3, but regulates NbNPR3 degradation via heat shock protein 90s (NbHSP90s). NbHSP90s bind to both NbNPR3 and βC1 and suppress SA signaling. This viral success strategy appears to be conserved as it is also documented for viral proteins encoded by two aphid-borne viruses. Our findings reveal an exquisite mechanism that facilitates the persistence of vector-borne plant viruses and provide important insights into the intricacies of the virus life cycle.